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GeneBe

5-116446797-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020796.5(SEMA6A):c.2909A>C(p.Gln970Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00573 in 1,613,124 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0059 ( 31 hom. )

Consequence

SEMA6A
NM_020796.5 missense

Scores

6
10

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.73
Variant links:
Genes affected
SEMA6A (HGNC:10738): (semaphorin 6A) Predicted to enable identical protein binding activity; signaling receptor binding activity; and transmembrane signaling receptor activity. Involved in cellular response to vascular endothelial growth factor stimulus; negative regulation of cell adhesion involved in sprouting angiogenesis; and negative regulation of signal transduction. Predicted to be integral component of membrane. Predicted to be active in extracellular space. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.007560551).
BP6
Variant 5-116446797-T-G is Benign according to our data. Variant chr5-116446797-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 718147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA6ANM_020796.5 linkuse as main transcriptc.2909A>C p.Gln970Pro missense_variant 19/19 ENST00000343348.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA6AENST00000343348.11 linkuse as main transcriptc.2909A>C p.Gln970Pro missense_variant 19/191 NM_020796.5 P4Q9H2E6-1

Frequencies

GnomAD3 genomes
AF:
0.00421
AC:
640
AN:
152168
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00125
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00720
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00584
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00691
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00470
AC:
1159
AN:
246662
Hom.:
5
AF XY:
0.00464
AC XY:
622
AN XY:
133916
show subpopulations
Gnomad AFR exome
AF:
0.00119
Gnomad AMR exome
AF:
0.00146
Gnomad ASJ exome
AF:
0.00722
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000986
Gnomad FIN exome
AF:
0.00771
Gnomad NFE exome
AF:
0.00720
Gnomad OTH exome
AF:
0.00334
GnomAD4 exome
AF:
0.00589
AC:
8600
AN:
1460838
Hom.:
31
Cov.:
31
AF XY:
0.00582
AC XY:
4231
AN XY:
726622
show subpopulations
Gnomad4 AFR exome
AF:
0.000747
Gnomad4 AMR exome
AF:
0.00159
Gnomad4 ASJ exome
AF:
0.00801
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000975
Gnomad4 FIN exome
AF:
0.00786
Gnomad4 NFE exome
AF:
0.00671
Gnomad4 OTH exome
AF:
0.00545
GnomAD4 genome
AF:
0.00420
AC:
640
AN:
152286
Hom.:
1
Cov.:
32
AF XY:
0.00396
AC XY:
295
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00125
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00720
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00584
Gnomad4 NFE
AF:
0.00691
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00659
Hom.:
7
Bravo
AF:
0.00379
TwinsUK
AF:
0.00405
AC:
15
ALSPAC
AF:
0.00908
AC:
35
ESP6500AA
AF:
0.00120
AC:
5
ESP6500EA
AF:
0.00733
AC:
62
ExAC
AF:
0.00445
AC:
539
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2023SEMA6A: BS2 -
Benign, criteria provided, single submitterclinical testingInvitaeMay 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.16
Cadd
Benign
23
Dann
Uncertain
0.99
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.95
D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.0076
T;T;T;T;T
MetaSVM
Benign
-0.95
T
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-2.2
N;N;N;N;N
REVEL
Benign
0.23
Sift
Uncertain
0.012
D;D;D;D;D
Sift4G
Benign
0.15
T;T;D;D;T
Polyphen
0.96, 0.94
.;.;D;P;.
Vest4
0.59
MVP
0.41
MPC
0.71
ClinPred
0.026
T
GERP RS
4.3
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200578077; hg19: chr5-115782493; COSMIC: COSV99030636; COSMIC: COSV99030636; API